US4028379A - Process for preparing 2-amino-2-alkylthio-1-nitroethylene compounds - Google Patents

Process for preparing 2-amino-2-alkylthio-1-nitroethylene compounds Download PDF

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Publication number
US4028379A
US4028379A US05/683,355 US68335576A US4028379A US 4028379 A US4028379 A US 4028379A US 68335576 A US68335576 A US 68335576A US 4028379 A US4028379 A US 4028379A
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United States
Prior art keywords
methylthio
nitro
ethylamino
nitroethylene
formula
Prior art date
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Expired - Lifetime
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US05/683,355
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English (en)
Inventor
George Raymond White
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Smith Kline and French Laboratories Ltd
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Smith Kline and French Laboratories Ltd
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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D213/28—Radicals substituted by singly-bound oxygen or sulphur atoms
    • C07D213/30—Oxygen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
    • C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
    • C07D233/64—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with substituted hydrocarbon radicals attached to ring carbon atoms, e.g. histidine
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
    • C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
    • C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
    • C07D277/22—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms
    • C07D277/26—Radicals substituted by sulfur atoms

Definitions

  • This invention relates to an improved process for the synthesis of amino compounds, in particular 2-amino-2-alkylthio-1-nitroethylenes and to the compounds so produced.
  • Such a process is particularly useful for the production of certain compounds which are intermediates for the production of histamine H 2 -antagonists.
  • a step in the process presently available for the production of many of these compounds involves the displacement of an alkylthio e.g., a methylthio group by an amino group and in certain cases, for example where the amine is not very reactive, this displacement may not take place easily. It is an object of the present invention to increase the efficiency of such displacement reactions.
  • R 1 is lower alkyl, lower alkoxy, 2,2,2-trifluoroethyl, (CH 2 ) n R 2 or HetCH 2 Z(CH 2 ) 2 ;
  • Het is an imidazole, thiazole, pyridine, isothiazole, oxazole, isoxazole, triazole or thiadiazole ring, which ring is optionally substituted by lower alkyl, hydroxyl, lower alkoxy, chlorine or bromine;
  • Z is sulphur or methylene;
  • n is an integer from 1 to 12; and
  • R 2 is hydroxy, lower alkoxy or lower alkylamino.
  • the compounds produced by the process of the present invention i.e., compounds of Formula III: ##STR2## are intermediates for the production of histamine H 2 - antagonists and may be converted to an H 2 -antagonist compound of Formula IV: ##STR3## by reaction thereof with an amine of formula R 3 NH 2 wherein R 3 is lower alkyl, lower alkoxy, 2,2,2-trifluoroethyl, (CH 2 ) n R 2 or HetCH 2 Z(CH 2 ) 2 but with the proviso that if R 1 is not HetCH 2 Z(CH 2 ) 2 then R 3 must be HetCH 2 Z(CH 2 ) 2 .
  • lower alkyl we mean an alkyl group containing from 1 to 4 carbon atoms.
  • the process of the present invention when carried out between equivalent amounts of the compounds of formulae I and II results in the production of the compound of Formula III without the formation of any significant amounts of the bis compound of Formula V: ##STR4## and this selectivity may in certain cases be desirable.
  • the process of the invention may, in general, be carried out under mild conditions. For example gradual addition of a solution of the amine of Formula II to a stirred solution of the compound of Formula I at a temperature of from 15°-40° C. normally results in production of the required compound of Formula III which may then be isolated from the reaction mixture and purified by conventional methods. The reaction has been found to proceed successfully even when using amines which are normally comparatively unreactive e.g., those of Formula II wherein R is alkoxy or 2,2,2-trifluoroethyl.
  • the compound of Formula I may be produced by treatment of the corresponding compound of Formula VI: ##STR5## wherein A has the above significance with an oxidizing agent such as hydrogen peroxide. This reaction may be carried out in a suitable solvent such as acetic acid.
  • A is most conveniently methyl.
  • the process is particularly useful for the production of compounds of Formula III wherein R 1 is alkoxy, (CH 2 ) n R 2 or Het CH 2 Z(CH 2 ) 2 .
  • H 2 -antagonist compounds which are all intermediates for H 2 -antagonists, may be reacted with a suitable amine to yield H 2 -antagonist compounds such as:
  • H 2 -antagonists of Formula IV act at histamine H 2 -receptors which as described by Black et al. (Nature, 1972, 236, 385) may be defined as those histamine receptors which are not blocked by "antihistamines" such as mepyramine but are blocked by burimamide. Blockade of histamine H 2 -receptors is of utility in inhibiting the biological actions of histamine which are not inhibited by "antihistamines”. Histamine H 2 -antagonists are useful, for example, as inhibitors of gastric acid secretion.
  • Example 1 shows the preparation of a starting material.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Thiazole And Isothizaole Compounds (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)
  • Pyridine Compounds (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
US05/683,355 1975-05-15 1976-05-05 Process for preparing 2-amino-2-alkylthio-1-nitroethylene compounds Expired - Lifetime US4028379A (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GB20628/75A GB1554153A (en) 1975-05-15 1975-05-15 Process for making 2-amino-2-alkylthionitroethylenes
UK20628/75 1975-05-15

Publications (1)

Publication Number Publication Date
US4028379A true US4028379A (en) 1977-06-07

Family

ID=10149067

Family Applications (1)

Application Number Title Priority Date Filing Date
US05/683,355 Expired - Lifetime US4028379A (en) 1975-05-15 1976-05-05 Process for preparing 2-amino-2-alkylthio-1-nitroethylene compounds

Country Status (10)

Country Link
US (1) US4028379A (enrdf_load_stackoverflow)
JP (1) JPS6058747B2 (enrdf_load_stackoverflow)
BE (1) BE841526A (enrdf_load_stackoverflow)
CA (1) CA1083159A (enrdf_load_stackoverflow)
DE (1) DE2621092C2 (enrdf_load_stackoverflow)
FR (1) FR2311003A1 (enrdf_load_stackoverflow)
GB (1) GB1554153A (enrdf_load_stackoverflow)
IE (1) IE43687B1 (enrdf_load_stackoverflow)
IL (1) IL49476A (enrdf_load_stackoverflow)
ZA (1) ZA762373B (enrdf_load_stackoverflow)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4169855A (en) * 1976-08-04 1979-10-02 Allen & Hansbury, Limited N'-derivatives of n-(2-mercapto-ethyl)-2-nitro-1,1-ethenediamine
US4200760A (en) * 1978-09-26 1980-04-29 Bristol-Myers Company Imidazolylalkylthioalkylamino-ethylene derivatives
EP0765870A3 (en) * 1995-09-01 1998-06-17 Rohm And Haas Company Broad-spectrum antimicrobially active compounds

Families Citing this family (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
ZA782129B (en) 1977-04-20 1979-03-28 Ici Ltd Hertocyclic derivatives
US4165378A (en) 1977-04-20 1979-08-21 Ici Americas Inc. Guanidine derivatives of imidazoles and thiazoles
EP0014057B1 (en) 1979-01-18 1985-01-02 Imperial Chemical Industries Plc Guanidine derivatives, processes for their manufacture and pharmaceutical compositions containing them
GB8415254D0 (en) * 1984-06-15 1984-07-18 Glaxo Group Ltd Amine derivatives
DE3886467T2 (de) * 1987-08-01 1994-06-01 Takeda Chemical Industries Ltd Alpha-ungesättigte Amine, ihre Herstellung und Verwendung.
GB8907700D0 (en) * 1989-04-05 1989-05-17 Fine Organics Ltd Preparation of substituted ethenes
EP0396830B1 (en) * 1989-05-10 1993-10-27 Council of Scientific and Industrial Research An improved process for the preparation of 1-substituted amino-1-substituted thio-2-nitro alkenes
FR3154258A1 (fr) 2023-10-13 2025-04-18 Psa Automobiles Sa Dispositif de stockage d’energie pour une batterie a onduleur distribue comportant un circuit secondaire de by-pass

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3876647A (en) * 1972-09-05 1975-04-08 Smith Kline French Lab Certain n-cyanoguanidines
GB1398426A (en) * 1972-09-05 1975-06-18 Smith Kline French Lab Heterocyclic substituted guanidines
US3953460A (en) * 1973-05-17 1976-04-27 Smith Kline & French Laboratories Limited Ethylene derivatives

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3876647A (en) * 1972-09-05 1975-04-08 Smith Kline French Lab Certain n-cyanoguanidines
GB1398426A (en) * 1972-09-05 1975-06-18 Smith Kline French Lab Heterocyclic substituted guanidines
US3953460A (en) * 1973-05-17 1976-04-27 Smith Kline & French Laboratories Limited Ethylene derivatives

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4169855A (en) * 1976-08-04 1979-10-02 Allen & Hansbury, Limited N'-derivatives of n-(2-mercapto-ethyl)-2-nitro-1,1-ethenediamine
US4200760A (en) * 1978-09-26 1980-04-29 Bristol-Myers Company Imidazolylalkylthioalkylamino-ethylene derivatives
EP0765870A3 (en) * 1995-09-01 1998-06-17 Rohm And Haas Company Broad-spectrum antimicrobially active compounds
US5883134A (en) * 1995-09-01 1999-03-16 Rohm And Haas Company Broad-spectrum antimicrobially active compounds

Also Published As

Publication number Publication date
IE43687L (en) 1976-11-15
ZA762373B (en) 1977-04-27
JPS51141806A (en) 1976-12-07
JPS6058747B2 (ja) 1985-12-21
BE841526A (fr) 1976-11-08
IL49476A (en) 1979-01-31
DE2621092A1 (de) 1976-11-25
CA1083159A (en) 1980-08-05
IE43687B1 (en) 1981-05-06
FR2311003A1 (fr) 1976-12-10
GB1554153A (en) 1979-10-17
FR2311003B1 (enrdf_load_stackoverflow) 1978-05-05
IL49476A0 (en) 1976-06-30
DE2621092C2 (de) 1986-06-19

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